Gene expression in Staphylococcus aureus skin infection

Gene expression in Staphylococcus aureus changes during infection to survive its host. Therefore, to find new strategies to combat staphylococcal infections, it is important to understand the mechanisms that this pathogen uses to adapt to its host and how the host responds to the presence of staphylococcal cells. We have reviewed two studies of gene expression in Staphylococcus aureus during skin infections, one study using a rabbit skin infection model and the other study using a diabetic skin infection model in mice. We compared the two gene expression profiles to find similarities and differences. Many genes did not show any differences in gene expression in S. aureus during the skin infection compared to the control groups. However,19 genes were upregulated in both systems include chaperones (e.g., groES, groEL, grpE, dnaK9), sodM, hrcA, sbi, and the gene encoding a cadmium-exporting ATPase protein. Also, four genes were downregulated in both systems including a gene that encodes a hydrolase and three genes for hypothetical proteins. Also, there was a group of genes expressed in different ways in the two systems. The gene expression of sarU, transcriptional regulators of the LysR family, Cro family, crp family, TetR family, tenA, and many hypothetical proteins were upregulated in the rabbit system but downregulated in the mouse system. The genes rps, rpl, rpm, and several others involved, for example, in translation and transcription were downregulated in the rabbit system but upregulated in the mouse system. Many genes that showed significant changes in overall gene expression in the rabbit model were unaffected in the mouse model. For example, in the rabbit skin infection model increased important gene regulators like agr and sarV, while some stress-response genes (e.g., sigB and lexA) were downregulated. The gene expression of several staphylococcal genes encoding virulence factors such as fibronectin-binding proteins, hemolysins, coagulases, complement inhibitory proteins, Emp, and many exotoxins were upregulated while clumping factor A was downregulated. Besides, some genes showed expression changes in the mouse model, but not in the rabbit model. For example, sarA, rot, ecb, ctsR, spx, many ribosomal proteins, and hypothetical proteins increased, while cap5k, lysE, rusA, and many hypothetical proteins decreased in the mouse model but they were unaffected in the rabbit model. On the other hand, the host responded to the S. aureus infection by inducing the expression of genes encoding host inflammatory cytokines, receptors, genes associated with neutrophil adhesion and migration, inflammation, and immune cell trafficking. In conclusion, the level of gene expression changed both in the pathogen and the host during the skin infection. The information of gene expression can make significant contributions to understand which genes are involved in the infection process, which can be targeted for antimicrobial chemotherapy.

Phage display identification of immunodominant epitopes and autoantibodies in autoimmune diseases

Phage display represents an invaluable tool to study autoimmune diseases. The side effects of immunosuppressive drugs for the treatment of autoimmune diseases raise awareness of the need to explore alternative therapeutic approaches such as antibodies and peptides. Therefore, phage display is an important technique for generating such molecules, so the purpose of this review is to determine the potential advantages of this technique in the research of autoimmune diseases. Many studies have also demonstrated the efficacy of phage display in identifying immunodominant epitopes of autoimmune diseases such as Goodpasture disease, immunologic thrombocytopenia, and systemic lupus erythematosus. Phage display peptide libraries have been screened with immunopurified autoantibodies from patients with autoimmune diseases. This makes it possible to more precisely locate the autoantibody binding sites, reveal a possible epitope sharing between the host and microbe, and identify a motif that mimics an antigenic structure such as that of dsDNA. Several studies have been conducted that have investigated the effectiveness of phage display in isolating autoantibody repertoires of autoantibodies against human epitopes. This allows the identification and design of antibody fragments (e.g., Fab, scFv, sdAb) that could block the binding of autoantibodies such as the deposition of IgG in the kidney and reduce the clinical signs of disease. In conclusion, phage display helps identify common epitopes and hotspot residues that can be potential therapeutic targets for the treatment of autoimmune diseases. This leads to a better understanding of the immunopathogenesis of autoimmune diseases and the development of more specific therapeutic strategies.

Bacterial molecular mimicry in autoimmune diseases

Bacterial molecular mimicry in autoimmune diseases is one of the leading mechanisms by which microorganisms may induce autoimmunity and survive in the host. The main purpose of the current study was to determine the main microbes that elicit autoimmune reactions through molecular mimicry and identify the most relevant approaches to investigate this mechanism. A classic example is the M protein of Streptococcus pyogenes, which induces antibody cross-reactivity with a cardiac protein and causes rheumatic fever. Another notable example is the protein from Porphyromonas gingivalis that closely resembles the human heat shock protein and accelerates atherosclerotic. There is evidence that antibodies against Helicobacter pylori CagA interact with different parts of smooth muscle and endothelial cells enhancing atherosclerotic vascular disease. Recently, one cause of infertility has been associated with Staphylococcus aureus molecular mimicry that triggers an antibody response that cross-reacts with human spermatozoa proteins. Further examples of bacterial molecular mimicry are associated with Chlamydia pneumoniae, Escherichia coli, Yersinia, and Salmonella. From the literature, the most widely used methods in this field are Basic Local Alignment Search Tool (BLAST), serological assays, and phage display. The subjects of particular concern are vaccine cross-reactivity and immunosuppressive drugs side-effects, therefore alternative approaches are needed. Such an approach is phage display where therapeutic antibody fragments obtained by this technique have been used in the treatment of autoimmune diseases by neutralizing the pathological effects of autoantibodies. Phage display libraries are constructed from the antibody repertoires of autoimmune disease patients. Antibody fragments without the Fc domain can not interact with Fc receptors and proteins of the complement system and trigger autoimmune diseases. Another approach is to block the Fc receptors. In conclusion, this review highlights key aspects of bacterial molecular mimicry to better understand the factors associated with autoimmune diseases and encourage further research in this field.